Computational Design and Directed Evolution

Dr H Adrian Bunzel

Research Associate
Groups of Ross Anderson and Adrian Mulholland
+44 (0) 117 331 2172

C102 – Biomedical Sciences Building
University Walk, Clifton BS8 1TD

Enzymes, designed by Nature over billions of years of evolution, accelerate their reactions with unequaled efficiency. To harness that power, I am employing computational enzyme design and experimental directed evolution to engineer novel enzymes.

Currently, I am using computational designing and directed evolution to introduce photosensitizer bindingsites into biocatalyst to afford photocatalytic enzymes (1). Furthermore, I am employing computational and experimental methods to dissect the dynamic (2) and electrostatic (3) origins of catalysis in designer enzymes.

(1) Artificial Photocatalytic Enzymes

(2) Dynamic Origins of Catalysis in Designer Enzymes
During my PhD with Prof. Donald Hilvert (ETH Zurich), I have improved a computationally designed Kemp eliminase by four orders of magnitude with directed evolution. Comparable to natural enzymes, rate enhancements were almost entirely enthalpic. Surprisingly, evolution introduced an activation heat capacity – resulting in curved Eyring plots – and signaling increased rigidity in the transition state ensemble. I am currently employing molecular dynamics simulations to identify the origins of that effect.

(3) Electrostatic Origins of Catalysis in Designer Enzymes


Bunzel HA; Kries H; Marchetti L; Mittl P; Mulholland A; Hilvert D; Emergence of a negative activation heat capacity during evolution of a computationally designed enzyme; submitted.

Bunzel HA; Garrabou X; Pott M; Hilvert D.; Speeding up enzyme discovery and engineering with ultrahigh-throughput methods; Curr Opin Struct Biol. 2018, 48, 149.

ORCID: 0000-0001-6427-368X

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